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TitleProgrammable genome editing in human cells using RNA-guided bridge recombinases.
Journal, issue, pagesScience, Vol. 391, Issue 6790, Page eadz1884, Year 2026
Publish dateMar 12, 2026
AuthorsOana Pelea / András Tálas / Javier Fernández Carrera / Nicolas Mathis / Lilly van de Venn / Charles D Yeh / Péter I Kulcsár / Kim F Marquart / Yanik Weber / Saskia E Gerecke / Isabelle F Harvey-Seutcheu / Dominic Mailänder / Moritz M Pfleiderer / Christelle Chanez / Jacob E Corn / Gerald Schwank / Martin Jinek /
PubMed AbstractSite-specific insertion of gene-sized DNA fragments remains an unmet need in the field of genome editing. IS110-family serine recombinases have recently been shown to mediate programmable DNA ...Site-specific insertion of gene-sized DNA fragments remains an unmet need in the field of genome editing. IS110-family serine recombinases have recently been shown to mediate programmable DNA recombination in bacteria by using a bispecific RNA guide (bridge RNA) that simultaneously recognizes target and donor sites. In this work, we have shown that the bridge recombinase ISCro4 is highly active in human cells and provided structural insights into its enhanced activity. Using plasmid- or all-RNA-based delivery, ISCro4 supports programmable multikilobase excisions and inversions and facilitates donor DNA insertion at genomic sites with efficiencies that exceed 6%. Last, we assessed ISCro4 specificity and off-target activity. These results establish a framework for the development of bridge recombinases as next-generation tools for editing modalities that are beyond the capabilities of current technologies.
External linksScience / PubMed:41642947
MethodsEM (single particle)
Resolution2.81 Å
Structure data

55572

9t56

EMDB-55572, PDB-9t56:
Cryo-EM structure of ISCro4-DBL-TBL-tDNA-dDNA synaptic complex
Method: EM (single particle) / Resolution: 2.81 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • citrobacter rodentium icc168 (bacteria)
KeywordsRECOMBINATION / Nucleic acid interaction / RNA binding / DNA binding / tetramer / recombinase

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